Ifistatin

Ifistatin Special Precautions

simvastatin

Manufacturer:

Unique Pharm

Distributor:

Uni Drug
Full Prescribing Info
Special Precautions
Simvastatin occasionally causes myopathy manifested as muscle pain, tenderness or weakness with creatine kinase (CK) above 10X the upper limit of normal (ULN). Myopathy sometimes takes the form of rhabdomyolysis with or without acute renal failure secondary to myoglobinuria, and rare fatalities have occurred. The risk of myopathy is increased by high levels of HMG-CoA reductase inhibitory activity in plasma. Predisposing factors for myopathy include advanced age (≥65 years), female gender, uncontrolled hypothyroidism, and renal impairment.
As with other statins, the risk of myopthy/rhabdomyolysis is dose related. In a clinical trial database in which 41,413 patients were treated with simvastatin, 24,747 (approximately 60%) of whom were enrolled in studies with a median follow-up of at least 4 years, the incidence of myopathy was approximately 0.03%, 0.08% and 0.61% at 20, 40 and 80 mg/day, respectively. In these trials, patients were carefully monitored and some interacting medicinal products were excluded. In a clinical trial in which patients with a history of myocardial infarction were treated with simvastatin 80 mg/day (mean follow-up 6.7 years), the incidence of myopathy was approximately 1.0% compared with 0.02% for patients on 20 mg/day. Approximately half of these myopthy cases occurred during the first year of treatment. The incidence of myopathy during each subsequent year of treatment was approximately 0.1%. The risk of myopathy is greater in patients on simvastatin 80 mg compared with other statin-based therapies with similar LDL-C-lowering efficacy. Due to the increased risk of myopathy, including rhabdomyolysis, particularly during the first year treatment, use of the 80-mg dose of simvastatin should be restricted to patients who have been taking simvastatin 80mg chronically (e.g. for 12 months or more) without evidence of muscle toxicity. Patients unable to achieve their LDL-C goal utilizing the 40-mg dose of simvastatin should not be titrated to the 80 mg dose, but should be placed on alternative LDL-C lowering treatments(s) that provides greater LDL-C lowering. In patients taking simvastatin 80 mg for whom an interacting agent is needed, a lower dose of simvastatin or an alternative statin-based regimen with less potential for drug-drug interactions should be used.
In a clinical trial in which patients at high risk of cardiovascular disease were treated with simvastatin 40 mg/day (median follow-up 3.9 years), the incidence of myopathy was approximately 0.05% for non-Chinese patients (n=7367) compared with 0.24% for Chinese patients (n=5468). While the only Asian population assessed in this clinical trial was Chinese, caution should be used when prescribing simvastatin to Asian patients and the lowest dose necessary should be employed.
Cases of myopathy/rhabdomyolysis have been observed with simvastatin coadministered with lipid modifying doses (>1 g/day) of niacin. In a clinical trial (median follow-up 3.9 years) involving patients at high risk of cardiovascular disease and with well-controlled LDL-C levels on simvastatin 40 mg/day with or without ezetimibe 10 mg, there was no incremental benefit on cardiovascular outcomes with the addition of lipid-modifying doses (>1 g/day) of niacin. Therefore, the benefit of the combined use of simvastatin with niacin should be carefully weighed against the potential risks of the combination. In addition, in this trial, the incidence of myopathy was approximately 0.24% for Chinese patients on simvastatin 40 mg or ezetimibe/simvastatin 10/40 mg compared with 1.24% for Chinese patients on simvastatin 40 mg or ezetimibe/simvastatin 10/40 mg coadministered with extended-release niacin/laropiprant 2 g/40 mg. While the only Asian population assessed in this clinical trial was Chinese, because the incidence of myopathy is higher in Chinese than in non-Chinese patients, coadministration of simvastatin with lipid modifying doses (>1 g/day) of niacin is not recommended in Asian patients.
All patients starting therapy with simvastatin or whose dose of simvastatin is being increased should be advised of the risk of myopathy and told to report promptly any unexplained muscle pain, tenderness or weakness. Simvastatin therapy should be discontinued immediately if myopathy is diagnosed or suspected.
The presence of these symptoms, and a CK level >10 times the upper limit of normal indicates myopathy. In most cases, when patients were promptly discontinued from treatment, muscle symptoms and CK increases resolved. Periodic CK determinations may be considered in patients starting therapy with simvastatin or whose dose is being increased. Periodic CK determinations are recommended for patients titrating to the 80 mg dose. There is no assurance that such monitoring will prevent myopathy.
Prescribing recommendations for interacting agents are summarized in the table as follows: (See table.)

Click on icon to see table/diagram/image

Liver dysfunction: Persistent increases in serum transaminases have occurred which fell slowly to pre treatment levels when drug treatment was interrupted or discontinued. It is recommended that liver function tests be performed before the initiation of treatment at 6 or 12 weeks, after initiation of therapy or elevation in dose, and periodically thereafter (i.e. semiannually). Should an increase in AST or ALT of three times the upper limit of normal or greater persist, withdrawal of therapy is recommended.
Skeletal muscle: Rare cases of rhabdomyolysis with acute renal failure secondary to myoglobinuria have been associated with Simvastatin therapy. Rhabdomyolysis has also been associated with other HMG-Co A reductase inhibitors when they were administered alone or concomitantly with immunosuppressive therapy, fibrates or erythromycin in seriously ill patients. Therapy should be temporarily withheld or discontinued in any patient with an acute, serious condition suggestive of a myopathy or having a risk factor predisposing to the development of renal failure secondary to rhabdomyolysis (e.g. severe infection, hypotension, major surgery, trauma, severe metabolic, endocrine and electrolyte discorders and uncontrolled seizures).
Simvastatin may occasionally cause myopathy, which is manifested as muscle pain or weakness associated with grossly elevated creatine kinase (CK) (more than 10 times the upper limit of normal).
Myopathy sometimes takes the form of rhabdomyolysis with or without acute renal failure secondary to myoglobinuria, and rare fatalities have occurred.
Endocrine function: Simvastatin does not reduce plasma cortisol concentration, impair adrenal reserve nor reduce basal plasma testosterone concentration as other HMG-Co A reductase inhibitors.
Caution should be exercised if an HMG-Co A reductase inhibitor or other agent used to lower cholesterol levels is administered to patients also receiving other drugs (e.g. ketoconazole, spironolactone, cimetidine) that may decrease the levels or activity of endogenous steroid hormones.
Pregnancy and Lactation: Safety in pregnant women has not been established. Simvastatin should be administered to women in childbearing age only when such patients are highly unlikely to conceive. It is not known whether Simvastatin is excreted in human milk. Because a small amount of another drug in this class is excreted in human milk and because of the potential for serious adverse reactions in nursing infants, women taking Simvastatin should not nurse their infants.
Paediatric use: Safety and effectiveness in paediatric patients have not been established.
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